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      Impact of the SARS‐CoV‐2 virus on male reproductive health

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          Abstract

          The coronavirus 2019 (COVID‐19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to more than 160 million infections and 3.5 million deaths globally. Men are disproportionately affected by COVID‐19, having more severe disease with higher mortality rates than women. Androgens have been implicated as the underlying cause for more severe disease, as the androgen receptor has been noted to upregulate the cell surface receptors that mediate viral cell entry and infection. Unfortunately, despite testosterone’s potential role in COVID‐19 prognosis, androgen deprivation therapy is neither protective nor a treatment for COVID‐19. Interestingly, the male reproductive organs have been found to be vulnerable in moderate to severe illness, leading to reports of erectile dysfunction and orchitis. COVID‐19 viral particles have been identified in penile and testis tissue, both in live patients who recovered from COVID‐19 and post mortem in men who succumbed to the disease. Although sexual transmission remains unlikely in recovered men, moderate to severe COVID‐19 infection can lead to germ cell and Leydig cell depletion, leading to decreased spermatogenesis and male hypogonadism. The objective of this review is to describe the impact of SARS‐CoV‐2 on male reproductive health. There are still many unanswered questions as to the specific underlying mechanisms by which COVID‐19 impacts male reproductive organs and the long‐term sequelae of SARS‐CoV‐2 on male reproductive health.

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          SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

          Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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            Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

            Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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              Gender Differences in Patients With COVID-19: Focus on Severity and Mortality

              Objective: The recent outbreak of Novel Coronavirus Disease (COVID-19) is reminiscent of the SARS outbreak in 2003. We aim to compare the severity and mortality between male and female patients with COVID-19 or SARS. Study Design and Setting: We extracted the data from: (1) a case series of 43 hospitalized patients we treated, (2) a public data set of the first 37 cases of patients who died of COVID-19 and 1,019 patients who survived in China, and (3) data of 524 patients with SARS, including 139 deaths, from Beijing in early 2003. Results: Older age and a high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. Age was comparable between men and women in all data sets. In the case series, however, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). In SARS patients, the gender role in mortality was also observed. The percentage of males were higher in the deceased group than in the survived group (P = 0.015). Conclusion: While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.
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                Author and article information

                Contributors
                ramasamy@miami.edu
                Journal
                BJU Int
                BJU Int
                10.1111/(ISSN)1464-410X
                BJU
                Bju International
                John Wiley and Sons Inc. (Hoboken )
                1464-4096
                1464-410X
                31 August 2021
                31 August 2021
                : 10.1111/bju.15573
                Affiliations
                [ 1 ] Department of Urology University of Miami Miami Florida USA
                Author notes
                [*] [* ] Correspondence: Ranjith Ramasamy, MD, 1150 NW 14 th Street, Ste 309, Miami, FL 33136, USA.

                e‐mail: ramasamy@ 123456miami.edu

                Author information
                https://orcid.org/0000-0002-6884-4299
                Article
                BJU15573
                10.1111/bju.15573
                8444635
                34402155
                f710b0aa-f894-4124-a095-4cdadbbdc518
                © 2021 The Authors BJU International © 2021 BJU International

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 13 July 2021
                : 10 June 2021
                : 11 August 2021
                Page count
                Figures: 2, Tables: 1, Pages: 8, Words: 15412
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.7 mode:remove_FC converted:16.09.2021

                Urology
                men's health,covid‐19,male fertility,testosterone,spermatogenesis
                Urology
                men's health, covid‐19, male fertility, testosterone, spermatogenesis

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